المؤلفون: Jina, Lee, Jinju, Kim, Jae-Hyung, Lee, Yong Min, Choi, Hyeonil, Choi, Hwan-Doo, Cho, Guang-Ho, Cha, Young-Ha, Lee, Eun-Kyeong, Jo, Byung-Hyun, Park, Jae-Min, Yuk

المصدر: International journal of molecular sciences. 23(21)

مصطلحات موضوعية: Mice, Phosphatidylinositol 3-Kinases, Sirtuin 1, Autophagy, Animals, Humans, Calcium-Calmodulin-Dependent Protein Kinase Kinase, Forkhead Transcription Factors, AMP-Activated Protein Kinases, Proto-Oncogene Proteins c-akt, Toxoplasma

الوصف: Sirtuin 1 (SIRT1) regulates cellular processes by deacetylating non-histone targets, including transcription factors and intracellular signalling mediators; thus, its abnormal activation is closely linked to the pathophysiology of several diseases. However, its function in

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::04a003fd183870e31d4ec30166bb04abTest
https://pubmed.ncbi.nlm.nih.gov/36362370Test

المؤلفون: Jixiu Jin, Wenjia Li, Tian Wang, Byung-Hyun Park, Sung Kwang Park, Kyung Pyo Kang

المصدر: Cells; Volume 11; Issue 9; Pages: 1477

مصطلحات موضوعية: Inflammation, Male, Nephritis, Sulfur Compounds, Acetylation, General Medicine, urologic and male genital diseases, Benzoates, Fibrosis, kidney fibrosis, Sirt6, β-catenin, acetylation, TGF-β1/Smad signaling pathway, Disease Models, Animal, Mice, Animals, Humans, Sirtuins, Female, Kidney Diseases, beta Catenin, Ureteral Obstruction

الوصف: Renal fibrosis is a significant pathologic change associated with progressive kidney disease. Sirt6 is an NAD+-dependent deacetylase and mono-ADP ribosyltransferase known to play diverse roles in the processes attendant to aging, metabolism, and carcinogenesis. However, the role of proximal tubule-specific Sirt6 in renal fibrosis remains elusive. This study investigates the effect of proximal tubule-specific Sirt6 knockdown on unilateral ureteral obstruction (UUO)-induced renal tubulointerstitial inflammation and fibrosis. Renal fibrosis in wild type and PT-Sirt6KO (Sirt6flox/flox; Ggt1-Cre+) mice was induced by UUO surgery. After seven days, histologic examination and Western blot analysis were performed to examine extracellular matrix (ECM) protein expression. We evaluated inflammatory cytokine and cell adhesion molecule expression after ureteral obstruction. The therapeutic effect of Sirt6 activator MDL-800 on UUO-induced tubulointerstitial inflammation and fibrosis was assessed. The loss of Sirt6 in the proximal tubules aggravated UUO-induced tubular injury, ECM deposition, F4/80 positive macrophage infiltration, and proinflammatory cytokine and chemokine expression. Sirt6 activator MDL-800 mitigated UUO-induced renal tubulointerstitial inflammation and fibrosis. In an in vitro experiment, MDL-800 decreases the transforming growth factor (TGF)-β1-induced activation of myofibroblast and ECM production by regulating Sirt6-dependent β-catenin acetylation and the TGF-β1/Smad signaling pathway. In conclusion, proximal tubule Sirt6 may play an essential role in UUO-induced tubulointerstitial inflammation and fibrosis by regulating Sirt6-dependent β-catenin acetylation and ECM protein promoter transcription.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::99158a0487f86c4dbbe0ddd343fa9436Test

المؤلفون: Min Yan Shi, Dae Ho Lee, In Hyuk Bang, Eun Ju Bae, Byung-Hyun Park, Chang Yeob Han

المصدر: Theranostics

مصطلحات موضوعية: 0301 basic medicine, Male, Medicine (miscellaneous), FOXO1, Pharmacology, miR-495, chemistry.chemical_compound, Mice, 0302 clinical medicine, Medicine, Sirtuins, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Cells, Cultured, biology, Sirt6, Forkhead Box Protein O1, Middle Aged, Liver, FoxO1, Sirtuin, Glucose-6-Phosphatase, lipids (amino acids, peptides, and proteins), Female, Phosphoenolpyruvate carboxykinase, Injections, Intraperitoneal, Research Paper, SIRT6, Adult, Statin, medicine.drug_class, Primary Cell Culture, 03 medical and health sciences, Young Adult, Animals, Humans, Cholesterol, business.industry, Activator (genetics), statin, Gluconeogenesis, nutritional and metabolic diseases, MicroRNAs, 030104 developmental biology, chemistry, Diabetes Mellitus, Type 2, biology.protein, Hepatocytes, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, 030217 neurology & neurosurgery

الوصف: Rationale: Statin, the most widely used medication in lowering cholesterol, is also associated with increased risk of type 2 diabetes, but its molecular basis remains unclear. Methods: Mice were injected intraperitoneally with statins alone or in combination with sirtuin (Sirt) 6 activator, and blood glucose levels were measured. Liver tissues from patients with statin use were analyzed for the expression of Sirt6. Results: Statin treatment up-regulated the hepatic expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, which was prevented by Sirt6 overexpression. Mechanistically, statin directly repressed Sirt6 expression by induction of microRNA (miR)-495, a novel inhibitor of Sirt6. Pathway analysis for predicted target genes of miR-495 recognized forkhead box protein (Fox)O1 as a key downstream signaling of Sirt6. Statin treatment increased the acetylation and protein stability of FoxO1, which was suppressed by Sirt6 overexpression. Inhibiting miR-495 recovered Sirt6 levels, blocking the ability of statin to increase FoxO1 mediated gluconeogenesis, and thus confirming the role of the miR-495/Sirt6/FoxO1 pathway in controlling gluconeogenesis. Moreover, the Sirt6 activator MDL801 prevented gluconeogenesis and hyperglycemia induced by statin in mice. Equally noteworthy was that human liver tissues obtained from statin users showed a significant decrease in Sirt6 protein levels compared to those of non-users. Conclusion: Statin induces miR-495 to suppress Sirt6 expression, which leads to enhancement of FoxO1-mediated hepatic gluconeogenesis. Thus, Sirt6 activation may offer a promising strategy for preventing statin-induced hyperglycemia.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b66517d6f16be10daac4079d5f51be1bTest
http://europepmc.org/articles/PMC7545997Test

المؤلفون: Yuancheng Mao, Chang Yeob Han, Lihua Hao, Younho Lee, Jung Beom Son, Hwangeun Choi, Mi Rin Lee, Jae Do Yang, Suk Kyun Hong, Kyung‐Suk Suh, Hee Chul Yu, Nam Doo Kim, Eun Ju Bae, Byung‐Hyun Park

المصدر: Hepatology (Baltimore, Md.)REFERENCES. 76(2)

مصطلحات موضوعية: Mice, Knockout, Mice, Hepatology, Liver, p21-Activated Kinases, Ischemia, NF-E2-Related Factor 2, Liver Diseases, Reperfusion Injury, Animals, Humans, Apoptosis, Phosphorylation

الوصف: p21-activated kinase 4 (PAK4), an oncogenic protein, has emerged as a promising target for anticancer drug development. Its role in oxidative stress conditions, however, remains elusive. We investigated the effects of PAK4 signaling on hepatic ischemia/reperfusion (I/R) injury.Hepatocyte- and myeloid-specific Pak4 knockout (KO) mice and their littermate controls were subjected to a partial hepatic I/R (HIR) injury. We manipulated the catalytic activity of PAK4, either through genetic engineering (gene knockout, overexpression of wild-type [WT] or dominant-negative kinase) or pharmacological inhibitor, coupled with a readout of nuclear factor erythroid 2-related factor 2 (Nrf2) activity, to test the potential function of PAK4 on HIR injury. PAK4 expression was markedly up-regulated in liver during HIR injury in mice and humans. Deletion of PAK4 in hepatocytes, but not in myeloid cells, ameliorated liver damages, as demonstrated in the decrease in hepatocellular necrosis and inflammatory responses. Conversely, the forced expression of WT PAK4 aggravated the pathological changes. PAK4 directly phosphorylated Nrf2 at T369, and it led to its nuclear export and proteasomal degradation, all of which impaired antioxidant responses in hepatocytes. Nrf2 silencing in liver abolished the protective effects of PAK4 deficiency. A PAK4 inhibitor protected mice from HIR injury.PAK4 phosphorylates Nrf2 and suppresses its transcriptional activity. Genetic or pharmacological suppression of PAK4 alleviates HIR injury. Thus, PAK4 inhibition may represent a promising intervention against I/R-induced liver injury.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a81a4dede041582a15b186885855bf8eTest
https://pubmed.ncbi.nlm.nih.gov/35108418Test

المؤلفون: Hyun-Woo, Kim, Ga-Hee, Ryoo, Hyun-Young, Jang, So-Young, Rah, Dong Hyun, Lee, Do-Kyun, Kim, Eun Ju, Bae, Byung-Hyun, Park

المصدر: Theranostics. 12(7)

مصطلحات موضوعية: Male, Mice, Inbred C57BL, Mice, Knockout, Mice, Animals, Humans, Sirtuins, Mast Cells, Prostate-Specific Antigen, NAD, Anaphylaxis, Cell Degranulation

الوصف: Nicotinamide adenine dinucleotide (NAD

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::f3bb0b16c78a710126a6a307813ce7b8Test
https://pubmed.ncbi.nlm.nih.gov/35547746Test

المؤلفون: Soo-Wan Chae, Su-Jin Jung, Byung-Hyun Park, Jae-Heon Yang, Sung-Hyen Lee, Do-Youn Jeong, Eun-Kyung Choi, You-Suk Kim, Ui-Jin Bae, Soo Hyun Park, Hyun-Ju Kim

المصدر: BMC Complementary Medicine and Therapies, Vol 20, Iss 1, Pp 1-8 (2020)
BMC Complementary Medicine and Therapies

مصطلحات موضوعية: Blood Glucose, Male, 0301 basic medicine, medicine.medical_treatment, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Insulin, Medicine, Prediabetes, Plasma glucose, Cross-Over Studies, C-Peptide, biology, Incremental area under the curve, Allium hookeri, lcsh:Other systems of medicine, Middle Aged, Female, Animal studies, Research Article, Adult, medicine.medical_specialty, 030209 endocrinology & metabolism, Oral glucose tolerance test, Placebo, Allium, Prediabetic State, 03 medical and health sciences, Double-Blind Method, Internal medicine, Republic of Korea, Humans, Aged, Glycemic, Glycated Hemoglobin, 030109 nutrition & dietetics, Triglyceride, Plant Extracts, business.industry, Glucose Tolerance Test, medicine.disease, biology.organism_classification, lcsh:RZ201-999, Clinical trial, Complementary and alternative medicine, chemistry, Hemoglobin A1c, business, Biomarkers

الوصف: Background Allium hookeri is widely consumed as a vegetable and herbal medicine in Asia. A. hookeri has been reported anti-inflammatory, anti-obesity, osteoblastic, anti-oxidant, and anti-diabetic effects in animal studies. We investigated the anti-diabetic effects of A. hookeri aqueous extract (AHE) in the Korean subjects. Methods Prediabetic subjects (100 ≤ fasting plasma glucose (FPG)

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::71e6b2236f7eb3488010cff1fb1f0fc7Test
http://link.springer.com/article/10.1186/s12906-020-03005-3Test

المؤلفون: Sang-A Lee, Usama Khamis Hussein, Woo Sung Moon, Myoung Ja Chung, Ho Lee, Keun Sang Kwon, Chan Young Kim, Asmaa Gamal Ahmed, Myoung Jae Kang, Ho Sung Park, Byung-Hyun Park, Sang Hoon Ha, See-Hyoung Park, Kyu Yun Jang, Zhongkai Zhang, Kyoung Min Kim

المصدر: Aging (Albany NY)

مصطلحات موضوعية: Male, SCRIB, Proteasome Endopeptidase Complex, Aging, Carcinogenesis, Immunoprecipitation, FAM83H, Kaplan-Meier Estimate, Biology, medicine.disease_cause, Disease-Free Survival, Mice, Gastrectomy, Stomach Neoplasms, In vivo, Cell Line, Tumor, medicine, Animals, Humans, cancer, beta Catenin, Cell Proliferation, Retrospective Studies, Protein Stability, Tumor Suppressor Proteins, Stomach, Carcinoma, Membrane Proteins, Proteins, Cancer, Cell Biology, Middle Aged, β-catenin, Prognosis, medicine.disease, Xenograft Model Antitumor Assays, medicine.anatomical_structure, Gastric Mucosa, Gene Knockdown Techniques, Catenin, Proteolysis, Cancer cell, Disease Progression, Cancer research, Female, stomach, Research Paper

الوصف: FAM83H primarily is known for its function in tooth development. Recently, a role for FAM83H in tumorigenesis, conjunction with MYC and β-catenin, has been suggested. Analysis of public data indicates that FAM83H expression is closely associated with SCRIB expression in human gastric cancers. Therefore, this study investigated the roles of FAM83H and SCRIB in 200 human gastric cancers and gastric cancer cells. In human gastric carcinomas, both the individual and combined expression patterns of the nuclear FAM83H and SCRIB were independent indicators of shorter survival of gastric carcinoma patients. In MKN-45 and NCI-N87 gastric cancer cells, the expression of FAM83H and SCRIB were associated with proliferation and invasiveness of cells. FAM83H-mediated in vivo tumor growth was attenuated with knock-down of SCRIB. Moreover, immunoprecipitation indicates that FAM83H, SCRIB, and β-catenin, form a complex, and knock-down of either FAM83H or SCRIB accelerated proteasomal degradation of β-catenin. In conclusion, this study has found that the individual and combined expression patterns of nuclear FAM83H and SCRIB are prognostic indicators of gastric carcinomas and further suggests that FAM83H and SCRIB are involved in the progression of gastric carcinomas by stabilizing β-catenin.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9a7cf6621609f6e15ddeddbc5f8e2c39Test
https://doi.org/10.18632/aging.103351Test

المؤلفون: Dami Park, Byung-Chul Oh, In Hyuk Bang, Oh Kwang Kwon, Eun Ju Bae, Byung-Hyun Park, Lihua Hao, Myung-Ja Chung, Sangkyu Lee

المصدر: Experimental and Molecular Medicine, Vol 51, Iss 9, Pp 1-11 (2019)
Experimental & Molecular Medicine

مصطلحات موضوعية: Male, X-Box Binding Protein 1, medicine.medical_specialty, XBP1, Clinical Biochemistry, Mice, Obese, lcsh:Medicine, Protein degradation, Biochemistry, Article, lcsh:Biochemistry, Transactivation, Mice, Non-alcoholic Fatty Liver Disease, Internal medicine, Nonalcoholic fatty liver disease, medicine, Animals, Humans, Sirtuins, lcsh:QD415-436, Molecular Biology, Mice, Knockout, biology, Chemistry, lcsh:R, Acetylation, Translational research, medicine.disease, Endoplasmic Reticulum Stress, Lipid Metabolism, Fatty Liver, Endocrinology, Gene Expression Regulation, Liver, Sirtuin, Proteolysis, Unfolded protein response, biology.protein, Hepatocytes, Molecular Medicine, Steatosis, Protein Processing, Post-Translational

الوصف: The active spliced form of X-box-binding protein 1 (XBP1s) is a key modulator of ER stress, but the functional role of its post-translational modification remains unclear. Here, we demonstrate that XBP1s is a deacetylation target of Sirt6 and that its deacetylation protects against ER stress-induced hepatic steatosis. Specifically, the abundance of acetylated XBP1s and concordant hepatic steatosis were increased in hepatocyte-specific Sirt6 knockout and obese mice but were decreased by genetic overexpression and pharmacological activation of Sirt6. Mechanistically, we identified that Sirt6 deacetylated a transactivation domain of XBP1s at Lys257 and Lys297 and promoted XBP1s protein degradation through the ubiquitin-proteasome system. Overexpression of XBP1s, but not its deacetylation mutant 2KR (K257/297R), in mice increased lipid accumulation in the liver. Importantly, in liver tissues obtained from patients with nonalcoholic fatty liver disease (NAFLD), the extent of XBP1s acetylation correlated positively with the NAFLD activity score but negatively with the Sirt6 level. Collectively, we present direct evidence supporting the importance of XBP1 acetylation in ER stress-induced hepatic steatosis.
Fatty liver disease: Regulatory protein link points to potential therapy Activating a protein that regulates cellular health could protect against fat accumulation during the onset of non-alcoholic fatty liver disease (NAFLD). A high-fat diet disrupts the endoplasmic reticulum (ER), a cellular membrane network responsible for synthesizing and processing proteins and fats, and can lead to NAFLD development. Previous studies found that a protein called XBP1s activates fat-related genes during NAFLD. Byung-Hyun Park and Eun Ju Bae at Chonbuk National University in Jeonbuk, South Korea, and co-workers, recently demonstrated that high levels of a regulatory protein called Sirt6 limits liver inflammation and ER stress during high-fat diets. Now, in experiments on mouse models and human liver cells, Park’s team have shown that Sirt6 reduces liver ER stress by modifying XBP1s. Encouraging Sirt6 activation may help protect against NAFLD progression.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cb9be61ec7796dc646b31b0cb71216e7Test
http://link.springer.com/article/10.1038/s12276-019-0309-0Test

المؤلفون: Byung-Hyun Park, Hua Jin, Ok-Hee Chai, Thi Van Nguyen, Soo Mi Kim, Ruo Yu Meng

المصدر: International Journal of Molecular Sciences
Volume 22
Issue 21
International Journal of Molecular Sciences, Vol 22, Iss 11486, p 11486 (2021)

مصطلحات موضوعية: Esophageal Neoplasms, medicine.disease_cause, chemistry.chemical_compound, Mice, Cell Movement, Antineoplastic Combined Chemotherapy Protocols, Biology (General), Spectroscopy, Chemistry, apoptosis, Drug Synergism, General Medicine, Cadherins, Computer Science Applications, esophageal squamous cell carcinoma, Paclitaxel, Matrix Metalloproteinase 9, Signal Transduction, Programmed cell death, QH301-705.5, Antineoplastic Agents, ursolic acid, Article, Catalysis, Inorganic Chemistry, Ursolic acid, In vivo, Cell Line, Tumor, medicine, Animals, Humans, Neoplasm Invasiveness, Physical and Theoretical Chemistry, Molecular Biology, Protein kinase B, QD1-999, Cell Proliferation, Glycogen Synthase Kinase 3 beta, Cell growth, Akt, Organic Chemistry, Forkhead Box Protein M1, FOXM1, Cell Cycle Checkpoints, Triterpenes, Apoptosis, Cancer research, Carcinogenesis, Proto-Oncogene Proteins c-akt

الوصف: Ursolic acid (UA), a pentacyclic triterpenoid extracted from various plants, inhibits cell growth, metastasis, and tumorigenesis in various cancers. Chemotherapy resistance and the side effects of paclitaxel (PTX), a traditional chemotherapy reagent, have limited the curative effect of PTX in esophageal cancer. In this study, we investigate whether UA promotes the anti-tumor effect of PTX and explore the underlying mechanism of their combined effect in esophageal squamous cell carcinoma (ESCC). Combination treatment with UA and PTX inhibited cell proliferation and cell growth more effectively than either treatment alone by inducing more significant apoptosis, as indicated by increased sub-G1 phase distribution and protein levels of cleaved-PARP and cleaved caspase-9. Similar to the cell growth suppressive effect, the combination of UA and PTX significantly inhibited cell migration by targeting uPA, MMP-9, and E-cadherin in ESCC cells. In addition, combination treatment with UA and PTX significantly activated p-GSK-3β and suppressed the activation of Akt and FOXM1 in ESCC cells. Those effects were enhanced by the Akt inhibitor LY2940002 and inverted by the Akt agonist SC79. In an in vivo evaluation of a murine xenograft model of esophageal cancer, combination treatment with UA and PTX suppressed tumor growth significantly better than UA or PTX treatment alone. Thus, UA effectively potentiates the anti-tumor efficacy of PTX by targeting the Akt/FOXM1 cascade since combination treatment shows significantly more anti-tumor potential than PTX alone both in vitro and in vivo. Combination treatment with UA and PTX could be a new strategy for curing esophageal cancer patients.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::08acf10a134dcd7bb399670e8ef5defaTest

المؤلفون: Hwangeui Cho, In Hyuk Bang, Eun Ju Bae, Byung-Hyun Park, Dami Park, Youngyi Lee

المصدر: Aging Cell

مصطلحات موضوعية: Male, SIRT6, Aging, Myeloid, Macrophage polarization, p300, M2 macrophage, GATA‐1, Mice, chemistry.chemical_compound, Adipocyte, medicine, Animals, Humans, Sirtuins, eosinophil, GATA1 Transcription Factor, acetylation, Activating Transcription Factor 1, Original Paper, Eosinophil differentiation, biology, Sirt6, Cell Differentiation, Original Articles, Cell Biology, M2 Macrophage, adipocyte beiging, Cell biology, Eosinophils, medicine.anatomical_structure, chemistry, Sirtuin, biology.protein, Deacetylase activity

الوصف: There is evidence emerging that exposure to cold temperatures enhances alternative activation of macrophages in white adipose tissue (WAT), which promotes adipocyte beiging and adaptive thermogenesis. Although we recently reported that NAD+‐dependent deacetylase sirtuin 6 (Sirt6) drives alternatively activated (M2) macrophage polarization, the role of myeloid Sirt6 in adaptive thermogenesis had remained elusive. In this study, we demonstrate that myeloid Sirt6 deficiency impaired both thermogenic responses and M2 macrophage infiltration in subcutaneous WAT (scWAT) during cold exposure. Moreover, the infiltration of Siglec‐F‐positive eosinophils in scWAT and Th2 cytokines levels was reduced in myeloid Sirt6 knockout mice. An ex vivo bone marrow‐derived cell culture experiment indicated that Sirt6 was required for eosinophil differentiation independent of its deacetylase activity. Data from our in vitro experiments show that Sirt6 acted as a transcriptional cofactor of GATA‐1, independent of its catalytic function as a deacetylase or ADP‐ribosyltransferase. Specifically, Sirt6 physically interacted with GATA‐1, and enhanced GATA‐1’s acetylation and transcriptional activity by facilitating its cooperation with p300. Overall, our results suggest that myeloid Sirt6 plays an important role in eosinophil differentiation and fat beiging/adaptive thermogenesis, which is at least in part due to its ability to bind GATA‐1 and stimulate its transcriptional activity.
Eosinophil infiltration into white adipose tissue has been found to be crucial for M2 macrophage polarization and adipose tissue browning upon cold exposure. We identify Sirt6 as an important regulator of eosinophil differentiation and thus adaptive thermogenesis by enhancing the acetylation and transcriptional activity of GATA‐1 by facilitating its cooperation with p300 acetyltransferase.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a839c23ccf66c9ce0c27806d59c44a6Test
https://doi.org/10.1111/acel.13418Test